Prosthetic heart valve formation

ABSTRACT

A prosthetic heart valve includes a base and a plurality of polymeric leaflets. Each leaflet has a root portion coupled to the base, and each leaflet has an edge portion substantially opposite the root portion and movable relative to the root portion to coapt with a respective edge portion of at least one of the other leaflets of the plurality of leaflets. Each leaflet includes) at least two polymers along at least one portion of the leaflet, and each leaflet has a composition gradient of each of the at least two polymers along at least one portion of the leaflet.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority under 35 USC §119(e) to U.S.Provisional Patent Application Ser. No. 61/667,267, filed on Jul. 2,2012, the entire contents of which is hereby incorporated by reference.

TECHNICAL FIELD

The following disclosure relates to replacement heart valves and, moreparticularly, to replacement heart valves including polymer leaflets.

BACKGROUND

Heart valve replacement is a widely used procedure in the treatment ofstructural heart disease. For example, heart valve replacement may beindicated when there is a narrowing of the native heart valve, commonlyreferred to as stenosis, or when the native valve leaks or regurgitates.Prosthetic heart valves used to replace these diseased valves includemechanical and tissue-based valves.

Tissue-based valves include leaflets made from biological tissue such asbovine pericardium or porcine pericardium. For use as valve leaflets,such xenograft tissues typically need to be fixed, usually byglutaraldehyde, and attached to a scaffold, usually by a suture. Theseprocesses can be labor intensive and time consuming and, given theirmanual nature, can be the source of some variability in valveperformance.

SUMMARY

A prosthetic heart valve replaces the function of a native heart valvesuch that the prosthetic valve regulates the flow of blood through theheart.

In one aspect, a prosthetic heart valve includes a base and a pluralityof polymeric leaflets. Each leaflet has a root portion coupled to thebase, and each leaflet has an edge portion substantially opposite theroot portion and movable relative to the root portion to coapt with arespective edge portion of at least one of the other leaflets of theplurality of leaflets. Each leaflet includes two or more polymers, andeach leaflet has a composition gradient of each of the at least twopolymers along at least one portion of the leaflet.

In some implementations, each leaflet has a substantially uniformthickness. In certain implementations, each leaflet has a decreasingthickness in a direction extending generally from the root portion tothe edge portion.

In some implementations, one of the at least two polymers is a firstlayer, another of the at least two polymers is a second layer, and eachof the layers extends in a direction generally from the root portion tothe edge portion. The thickness of one or more of the first and secondlayers can decrease in the direction generally from the root portion tothe edge portion.

In some implementations, the polymeric leaflet has a layer structurewith an interior layer disposed between external layers and having acomposition different from the composition of each of the externallayers. Each of the external layers can have a higher hardsegment-to-soft segment ratio compared to the interior layer to reduce,for example, the likelihood of tack (auto adhesion) between coaptingleaflets.

In some implementations, the external layer facing the aorta isdifferent from the external layer facing the ventricles.

In certain implementations, the composition gradient is a substantiallycontinuous increase in the ratio of one of the at least two polymers toanother one of the at least two polymers along the at least one portionof the leaflet. In some implementations, the composition gradient is apattern of the at least two polymers along the at least one portion ofthe leaflet. Additionally or alternatively, each leaflet has a stiffnessgradient along the at least one portion of the leaflet corresponding tothe composition gradient. For example, each leaflet can have acomposition gradient and a stiffness gradient in a direction extendingfrom the root portion to the edge portion and/or in a directionextending along a thickness of the leaflet. In certain implementations,each leaflet has a maximum thickness of 100 μm or less.

In some implementations, each of the at least two polymers hasrespective hard segments and soft segments and the ratio of hardsegments to soft segments in one of the at least two polymers is higherthan the ratio of hard segments to soft segments in another one of theat least two polymers. For example, each of the at least two polymerscan be a respective block polymer (e.g., a segmented block copolymer, alinear alternating multiblock copolymer, a triblock terpolymer, orasymmetric tetrablock terpolymers). The hard and soft segments of therespective block polymers can have the same molecular structure. Incertain implementations, the hard segments of the respective blockpolymers include methylene diisocyantate and butane diol. The softsegment of each respective block polymer can be synthesized fromoligomer diols, as an example

In certain implementations, the soft segment of each block polymers is acopolymer of a first monomer and a second monomer and the comonomerratio of the first monomer to the second monomer is varied incombination with the hard segment to soft segment ratio. The firstmonomer can be dimethyl siloxane and the second monomer can behexamethylene carbonate. In some implementations, the soft segments ofeach block polymer are synthesized from oligomer diols. In certainimplementations, the soft segments of each block polymer includepolydimethylsiloxane. The soft segments of each of the first and secondsegmented block copolymers can be hydrophilic. For example, the softsegments of each of the block polymers can be hydrophobic (e.g.,polydimethylsiloxane). In some implementations, the block polymers areeach thermoplastic elastomers.

In some implementations, one or more of the at least two polymers is apolyurethane block polymer and/or a polyurethane urea block polymer.

In certain implementations, one or more of the at least two polymers isone or more of the following: polycarbonate urethane;poly(dimethylsiloxane urethane); and poly(isobutylene urethane).

In some implementations, one of the at least two polymers is a surfacecoating disposed over at least a portion of another one or more of theat least two polymers, along at least one side of the leaflet extendingfrom the root portion to the edge portion. The surface coating can be apolyurethane with surface active end groups and/or a polyurethane ureawith surface active end groups. In some implementations, the surfacecoating is polyurethane and/or polyurethane urea with polyethylene oxidesoft segments. Additionally or alternatively, the surface coating can bea drug-releasing layer. Additionally or alternatively, the surfacecoating can have a different elastic modulus, compared to the one ormore polymers that it covers.

In certain implementations, each of the at least two polymers hasrespective hard and soft segments, the hard and soft segments of thesurface coating having the same molecular structure as the respectivehard and soft segments of the other of the at least two polymers, andthe surface coating includes surface active end groups. The surfaceactive end groups can include non-polar surface active end groups—e.g.,one or more of the following: fluorocarbon, dimethylsiloxane, andhydrocarbon. Additionally or alternatively, the surface active endgroups include polar surface active end groups. In some implementations,the surface active end groups include glycosaminoglycan and/orpolysaccharides. In certain implementations, the surface active endgroups include polyethylene oxide, hyaluronic acid, and heparin.

In some implementations, a skirt is disposed about the base. The skirtcan reduce and, in some cases, prevent paravalvular leaks. The basedefines a concentric passage therethrough, and the skirt iseccentrically arranged relative to the concentric passage of the base.The skirt can include one or more of the at least two polymers, and canbe integral with the base.

In certain implementations, the base defines a passage therethrough andthe plurality of leaflets are disposed within the passage. The base caninclude one or more of the at least two polymers. Additionally oralternatively, the base can include a stent (e.g., a self-expandablestent or a balloon-expandable stent) at least partially embedded in oneor more of the at least two polymers. In some implementations, the baseis substantially cylindrical, and the base has a height of about 5 mm toabout 20 mm.

In some implementations, the plurality of leaflets includes threeleaflets movable between an open position permitting flow of fluid pastthe prosthetic heart valve and a closed position substantiallyrestricting flow past the prosthetic heart valve.

In certain implementations, each of the plurality of leaflets furtherincludes fibers at least partially embedded in one or more of the atleast two polymers. The fibers can be oriented to achieve certainmechanical properties (e.g., stiffness). This includes fiberorientations resulting in anisotropic mechanical properties. Each of thefibers can extend substantially parallel or substantially perpendicularto a direction extending from the root portion to the edge portion ofthe respective leaflet. Additionally or alternatively, a first portionof the fibers can extend substantially parallel to a direction extendingfrom the root portion to the edge portion of the respective leaflet anda second portion of the fibers can extend substantially perpendicular toa direction extending from the root portion to the edge portion of therespective leaflet. In some implementations, the leaflets have one ormore anisotropic mechanical properties (e.g., stiffness). In certainimplementations, the fibers are substantially randomly embedded in oneor more of the first and second polymers.

In some implementations, the fibers include one or more of thefollowing: an ultra-high-molecular-weight polyethylene, liquidcrystalline polymer, and NiTi wire.

In another aspect, a prosthetic heart valve includes a base and aplurality of polymeric leaflets. Each leaflet has a root portion coupledto the base, and each leaflet has an edge portion substantially oppositethe root portion and movable relative to the root portion to coapt witha respective edge portion of at least one of the other leaflets of theplurality of leaflets. Each leaflet includes a polymer and fibers atleast partially embedded in the polymer.

In some implementations, the base defines a substantially cylindricalpassage extending therethrough, and the plurality of leaflets isdisposed in the cylindrical passage.

In certain implementations, the fibers are substantially parallel to aradial direction or a circumferential direction of the cylindricalpassage.

In some implementations, the fibers are arranged in a matrix with atleast a portion of the fibers oriented in a direction substantiallyparallel to a radial direction of the cylindrical passage and at least aportion of the fibers oriented in a direction substantially parallel toa circumferential direction of the cylindrical passage.

In certain implementations, the leaflets have one or more anisotropicmechanical properties (e.g., stiffness).

In some implementations, the fibers are substantially randomly embeddedin the polymer.

The fibers can include one or more of the following: a polyester, anultra-high-molecular-weight polyethylene, liquid crystalline polymer,and NiTi wire.

In yet another aspect, a method of forming a prosthetic heart valveincludes forming a base defining a substantially cylindrical passagetherethrough, forming a plurality of leaflets, and coupling each of theplurality of leaflets to the base. Each leaflet has a root portion andan edge portion substantially opposite the root portion. Each leafletincludes at least two polymers, and each leaflet has a compositiongradient of the at least two polymers along at least one portion of theleaflet. The root portion of each leaflet is coupled to the base suchthat each respective edge portion is substantially opposite the rootportion and movable relative to the root portion to coapt with arespective edge portion of at least one of the other leaflets of theplurality of leaflets.

In certain implementations, forming the base includes applying one ormore of the at least two polymers to at least one portion of a stent.For example, forming the base can include one or more of spray coating,dip coating, and vacuum forming one or more of the at least two polymersto at least one portion of a stent and/or to a mold. The at least twopolymers can be dried and, in implementations in which a mold is used,the base can be removed from the mold. In some implementations, dipcoating one or more of the at least two polymers on a mold includesrepeatedly dipping the mold into one or more polymer solutions.Additionally or alternatively, dip coating one or more of the at leasttwo polymers on the mold includes masking at least a portion of themold.

In certain implementations, forming the plurality of leaflets includesspray coating one or more of the at least two polymers on a mold. Spraycoating one or more of the at least two polymers on the mold can includeapplying the one or more of that at least two polymers as a multi-layerspray coating. Additionally or alternatively, spray coating one or moreof the at least two polymers on the mold can include spray coating oneor more of the at least two polymers on a mandrel disposed in thesubstantially cylindrical passage defined by the base.

In some implementations, spray coating the at least two polymers on themold includes controlling the ratio of one of the at least two-polymersto another one of the at least two-polymers along various locationsalong the mold. In certain implementations, spray coating the at leasttwo polymers on the mold includes controlling the thickness of one ormore of the at least two polymers at various locations along the mold.

In some implementations, spray coating one or more of the at least twopolymers on the mold includes delivering one of the at least twopolymers from a first spray head and delivering another one of the atleast two polymers from a second spray head. Additionally oralternatively, spray coating one or more of the at least two polymers onthe mold can include changing the position of the mold relative to thefirst and second spray heads. In certain implementations, spray coatingone or more of the at least two polymers on the mold comprisesdelivering one or more of the at least two polymers through athree-dimensional printing system, air spraying one or more of the atleast two polymers on the mold, and/or electrostatically spraying one ormore of the at least two polymers on the mold.

In certain implementations, forming the plurality of leaflets includesdip coating the one or more of the at least two polymers on a mold. Dipcoating one or more of the at least two polymers on the mold can includerepeatedly dipping the mold in one or more polymer solutions, eachpolymer solution comprising a solvent and one or more of the at leasttwo polymers. One or more of the at least two polymers can be dried onthe mold between successive dips of the mold in the one or more polymersolutions. In some implementations, the thickness and/or stiffness ofthe leaflet is controlled by controlling a dip rate of the mold into theone or more polymer solutions. Additionally or alternatively, thethickness and/or stiffness of the leaflet can be controlled bycontrolling an evaporation rate of one or more of the solvents in therespective polymer solutions.

In some implementations, dip coating one or more of the at least twopolymers on the mold includes dip coating one or more of the at leasttwo polymers on a mandrel disposed in the substantially cylindricalpassage defined by the base.

In certain implementations, dip coating the at least two polymers on themold includes controlling the ratio of one of the at least two polymersto another one of the at least two polymers along various locationsalong the mold and/or controlling the thickness of one or more of the atleast two polymers at various locations along the mold.

In some implementations, dip coating the at least two polymers on themold includes masking at least a portion of the mold.

In certain implementations, dip coating the at least two polymers on themold includes partially submerging the mold in a polymer solutioncomprising a solvent and one or more of the at least two polymers.

In some implementations, forming the plurality of leaflets comprisesvacuum forming one or more of the at least two polymers on a mold. Forexample, one or more of the at least two polymers can be a film.

In certain implementations, forming the plurality of leaflets furtherincludes cutting at least a portion of one or more of the at least twopolymers. Cutting at least a portion of one or more of the at least twopolymers can include directing one or more lasers at one or more of theat least two polymers. Additionally or alternatively, cutting at least aportion of one or more of the at least two polymers includes directing ablade at one or more of the at least two polymers.

In some implementations, forming the plurality of leaflets includesarranging a wall in the substantially cylindrical passage and applyingthe at least two polymers on either side of substantially planarsurfaces of the wall. The plurality of leaflets can be formed byremoving the wall from the substantially cylindrical passage. In certainimplementations, forming the plurality of leaflets includes removingexcess amounts of one or more of the at least two polymers on eitherside of the substantially planar surfaces of the wall. The wall can be ashim and/or the wall can include a thick portion and a thin portion suchthat the spacing between the plurality of formed leaflets is variablefrom the base to a center portion of the substantially cylindricalpassage.

In certain implementations, coupling the root portion of each of theplurality of leaflets to the base includes applying (e.g., spraycoating) one or more of the at least two polymers between the rootportion of each of the plurality of leaflets and the base.

In some implementations, a surface coating (e.g., a polyurethane withsurface active end groups) is applied over at least a portion of one ormore of the at least two polymers. In certain implementations, the atleast two polymers and the surface coating each include respective hardand soft segments, the hard and soft segments of the at least twopolymers and the surface coating have the same molecular structure, andthe surface coating further includes surface active end groups.

In certain implementations, forming the plurality of leaflets includesat least partially embedding a plurality of fibers in one or more of theat least two polymers. For example, forming the plurality of leafletscan include arranging each of the fibers in a direction substantiallyparallel or substantially perpendicular to a direction extending fromthe root portion to the edge portion of the respective leaflet. In someimplementations, forming the plurality of leaflets further includesarranging a first portion of the fibers in a direction extendingsubstantially parallel to a direction extending from the root portion tothe edge portion of the respective leaflet and a second portion of thefibers extending in a direction substantially perpendicular to adirection extending from the root portion to the edge portion of therespective leaflet. In certain implementations, forming the plurality ofleaflets further includes arranging the plurality of fibers in eachrespective leaflet such that each leaflet has one or more anisotropicmechanical properties (e.g., stiffness). In some embodiments, the fibersinclude one or more of an ultra-high-molecular-weight polyethylene, aliquid crystalline polymer, and a NiTi wire.

Implementations can include one or more of the following advantages.

In some implementations, prosthetic heart valves include a plurality ofpolymeric leaflets, each including a composition gradient of at leasttwo polymers along a portion of each leaflet. This composition gradientof each of the at least two polymers can improve the durability of theleaflets with respect to leaflets formed of a single polymer.Additionally or alternatively, this composition gradient of the at leasttwo polymers can improve the hemodynamic performance (e.g., by matchingnatural hemodynamic performance and/or through improved durability) ofeach leaflet as compared to leaflets formed of a single polymer at leastbecause the composition gradient allows each leaflet to have a desiredstiffness profile. In some instances, the composition gradient canreduce the overall thickness of each leaflet as compared to leafletsformed of a single polymer or biological tissue such that a prostheticheart valve including polymeric leaflets having this compositiongradient have smaller delivery profiles for transcatheter delivery.

In certain implementations, prosthetic heart valves include a pluralityof polymeric leaflets coupled to a base without the use of sutures. Ascompared to valves that require the use of sutures to secure leaflets,these sutureless prosthetic heart valves can be less labor intensive toproduce and can have less manufacturing variability. Additionally oralternatively, as compared to valves that require the use of sutures tosecure leaflets, these sutureless prosthetic heart valves can exhibitimproved durability.

In some implementations, prosthetic heart valves include a plurality ofleaflets, each leaflet including fibers at least partially embedded in apolymer. The fibers can be arranged along each leaflet to providesupport and/or desired mechanical properties (e.g., anisotropicmechanical properties) to each leaflet. In some instances, these fiberscan facilitate the use of a thinner layer of the polymer as compared topolymeric leaflets formed without these fibers. Such thinner layers canfacilitate that formation of prosthetic heart valves having smallerdelivery profiles for transcatheter delivery.

In certain implementations, the prosthetic heart valves include aplurality of polymeric leaflets formed of at least two polymers, one ofthe at least two polymers having hard and soft segments having the samemolecular structure as hard and soft segments of another one of the atleast two polymers, with the ratio of hard segments to soft segments inone of the at least two polymers being higher than the ratio of hardsegments to soft segments in another one of the at least two polymers.The use of two polymers having the same molecular structure can reducethe likelihood of delamination or other mechanical failure of thepolymeric leaflets while facilitating formation of the leaflets withvariable stiffness from a root portion to an edge portion.

In certain implementations, the prosthetic heart valves include aplurality of polymeric leaflets formed of at least two polymers, one ofthe at least two polymers having hard and soft segments having a certainmolecular structure and another one of the at least two polymers havingeither the same hard segment but different soft segment or differenthard segment but same soft segment. (e.g. polyisobutylene polyurethane(PIBU) and/or poly(styrene-block-isobutylene-block-styrene (SIBS)).Since these polymers have a common hard segment or soft segment, coatingone layer over a second layer will have eliminated the possibility ofdelamination because of the molecular miscibility as a result of thecommon structure. The use of two polymers having a common hard segmentor soft segment structure can reduce the likelihood of delamination orother mechanical failure of the polymeric leaflets while facilitatingformation of the leaflets with variable stiffness from a root portion toan edge portion. Additionally or alternatively, the use of two polymershaving a common hard segment or soft segment structure can facilitatecontrol of the mechanical properties and surface properties of thedevice.

In some implementations, the prosthetic heart valves are easier tomanufacture, are more reproducible, and have a lower height as comparedto mechanical heart valves and/or heart valves at least partially formedfrom biological tissue.

The details of one or more implementations of the invention are setforth in the accompanying drawings and the description below. Otherfeatures, objects, and advantages of the invention will be apparent fromthe description and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of a prosthetic heart valve.

FIG. 2 is a cross-sectional view of the prosthetic heart valve of FIG.1, along line 2-2.

FIG. 3 is a close-up of a cross-section of a polymeric leaflet of theprosthetic heart valve of FIG. 2 along circle 3.

FIG. 4A is a schematic illustration of repeated hard segments and softsegments of a polymer forming a leaflet of a prosthetic heart valve.

FIG. 4B is a schematic illustration of the polymer of FIG. 4A having afirst ratio of hard segments to soft segments.

FIG. 4C is a schematic illustration of the polymer of FIG. 4A having asecond radio of hard segments to soft segments.

FIGS. 5A-5D are schematic illustrations of steps of spray forming in theformation of a prosthetic heart valve.

FIG. 6 is a close-up of a cross-section of a polymeric leaflet of aprosthetic heart valve.

FIG. 7 is a close-up of a cross-section of a polymeric leaflet of aprosthetic heart valve.

FIG. 8 is a close-up of a cross-section of a polymeric leaflet of aprosthetic heart valve.

FIG. 9 is a side view of a prosthetic heart valve.

FIG. 10 is a top view of the prosthetic heart valve of FIG. 9.

FIG. 11 is a cross-sectional view of the prosthetic valve of FIG. 9along line 11-11.

FIGS. 12A-D are schematic illustrations of steps of spray forming in theformation of a prosthetic heart valve.

FIGS. 13A-B are schematic illustrations of steps of spray forming in theformation of prosthetic heart valve.

FIGS. 14A-C are schematic illustrations of steps of dip coating in theformation of a prosthetic heart valve.

FIGS. 15A-C are schematic illustrations of steps of vacuum forming inthe formation of a prosthetic heart valve.

FIG. 16 is a perspective view of a prosthetic heart valve includingfiber reinforced leaflets.

FIG. 17 is a perspective view of a prosthetic heart valve includingfiber reinforced leaflets.

FIG. 18 is a top view of a mold for forming fiber reinforced leaflets.Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Referring to FIGS. 1-3 a prosthetic heart valve 10 includes a base 12defining a substantially cylindrical passage 13 and a plurality ofpolymeric leaflets 14 a,b,c disposed along the substantially cylindricalpassage 13. Each polymeric leaflet 14 a,b,c includes a respective rootportion 16 a,b,c coupled to the base 12 and a respective edge portion 18a,b,c movable relative to the root portion 16 a,b,c to coapt with theedge portions of the other polymeric leaflets along the coaptationregion 20. It should be appreciated that the prosthetic heart valve 10can be any type of heart valve (e.g., a mitral valve or an aorticvalve).

In use, the prosthetic heart valve 10 is implanted (e.g., surgically orthrough transcatheter delivery) in a mammalian heart. The edge portions18 a,b,c of the polymeric leaflets 14 a,b,c move into coaptation withone another in a closed position to substantially restrict fluid fromflowing past the prosthetic heart valve 10 in a closed position. Theedge portions 18 a,b,c, of the leaflets 14 a,b,c move away from oneanother to an open position permitting fluid to flow past the prostheticheart valve 10. Movement of the leaflets 14 a,b,c between the closed andopen positions substantially approximates the hemodynamic performance ofa healthy natural valve.

As described in further detail below, the polymeric leaflets 14 a,b,care formed from a combination of at least two polymers, which can bearranged along each respective polymeric leaflets 14 a,b,c to facilitateachievement of a desired hemodynamic performance of the valve 10 throughlong periods of use. As also described in further detail below, thepolymeric leaflets 14 a,b,c can be attached to the base 12 without theuse of sutures, which can reduce the time and labor resources requiredto make the valve and can reduce valve-to-valve variability inhemodynamic performance.

The base 12 includes a frame 22 disposed in a polymer layer 24. Thepolymer layer 24 secures the respective root portions 16 a,b,c of thepolymeric leaflets 14 a,b,c to the base 12. The polymer layer 24 canform a substantially continuous surface with the respective rootportions 16 a,b,c of the polymeric leaflets 14 a,b,c. This can reducethe likelihood of stress concentrations at the junction of therespective root portions 16 a,b,c and the base 12. Additionally oralternatively, the polymer layer 24 can be disposed between each of thepolymeric leaflets 14 a,b,c and the frame 22 such that the polymer layer24 protects the polymeric leaflets 14 a,b,c from inadvertent contactwith the frame 22 (e.g., as can occur through eccentric deformation ofthe prosthetic heart valve 10 on a calcium deposit present at theimplantation site).

The frame 22 is substantially cylindrical such that the outer surface ofthe base 12 is substantially cylindrical and the polymer layer 24disposed on the frame 22 forms the substantially cylindrical passage 13.The frame can be metal and, additionally or alternatively, the frame 22can provide a radial force sufficient to at least partially secure thevalve 10 in place at the implantation site. In some implementations, theframe 22 is radially expandable from a collapsed position (e.g., fortranscatheter delivery) to an expanded position (e.g., for positioningat the implantation site). For example, the frame 22 can be aself-expandable stent or a balloon-expandable stent.

The frame 22 is completely disposed in the polymer layer 24, with thepolymer layer 24 forming a contoured outer surface of the valve 10.However, in some implementations, the frame 22 is partially disposed inthe polymer layer 24. In certain implementations, the polymer layer 24is applied to the frame 22 to form a substantially smooth inner and/orouter surface of the valve 10.

The polymer layer 24 and the leaflets 14 a,b,c, are formed of one ormore polymers having the same or substantially the same chemicalcomposition, which can reduce the likelihood of delamination and/orother types of degradation at the juncture of the polymer layer 24 andthe root portions 16 a,b,c of the polymeric leaflets 14 a,b,c. Forexample, the polymer layer 24 and/or the polymeric leaflets 14 a,b,c canbe formed of a first polymer and a second polymer, the first polymerhaving hard and soft segments having a certain molecular structure andthe second polymer having either the same hard segment but differentsoft segment or different hard segment but same soft segment (e.g.polyisobutylene polyurethane (PIBU) and/orpoly(styrene-block-isobutylene-block-styrene (SIBS)). Since thesepolymers have a common hard segment or soft segment, coating one layerover a second layer will reduce (e.g., eliminate) the possibility ofdelamination because of the molecular miscibility as a result of thecommon structure. The use of two polymers having a common hard segmentor soft segment structure can reduce the likelihood of delamination orother mechanical failure of the polymeric leaflets 14 a,b,c whilefacilitating formation of the leaflets with variable stiffness from aroot portion to an edge portion. Additionally or alternatively, the useof two polymers having a common hard segment or soft segment structurecan facilitate control of the mechanical properties and surfaceproperties of the device. The polymers in the polymer layer 24 and theleaflets 14 a,b,c are described in further detail below.

Given that the root portions 16 a,b,c are secured to the polymer layer24 and, thus, the base 12 without the use of sutures, the base 12 can beformed without support portions typically required on sutured valves.This can facilitate formation of the prosthetic heart valve 10 with alower overall height as compared to sutured valves. Such lower overallheight can improve the hemodynamic performance of the prosthetic heartvalve as compared to valves having larger overall heights. Additionallyor alternatively, the lower overall height facilitated by the formationof the prosthetic heart valve 10 without sutures can improve thephysiological performance of the prosthetic heart valve 10 as comparedto valves having larger overall heights. For example, the base 12 candefine an overall height of the prosthetic heart valve 10 and the heightof the base 12 can sized such that the coronary ostium is not covered bythe prosthetic heart valve 10 at the implantation site. This can, forexample, reduce the likelihood of disrupting normal electrical signalingin the heart. In some implementations, the base 12 has an overall heightof about 5 mm to about 20 mm, depending on the diameter of thecylindrical valve body.

The polymeric leaflets 14 a,b,c each have a substantially uniformthickness and a composition gradient of a first polymer 26 and a secondpolymer 28 along a length of the leaflet extending from each respectiveroot portion 16 a,b,c to the respective edge portion 18 a,b,c. Asdescribed in detail below, the first polymer 26 and the second polymer28 can be block polymers each having the same molecular structure butdifferent ratios of hard segments to soft segments such that the firstpolymer 26 is stiffer than the second polymer 28. Thus, the compositiongradient of the first polymer 26 and the second polymer 28 can be anincrease (e.g., a substantially continuous increase) in the ratio of thesecond polymer 28 to the first polymer 26 in a direction extendinggenerally from the root portion 16 a,b,c to the edge portion 18 a,b,c ofeach respective leaflet 14 a,b,c such that each leaflet is stiffertoward the root portion 16 a,b,c and more flexible toward the edgeportion 18 a,b,c. It should be appreciated that the polymeric leaflets14 a,b,c are described as including the first polymer 26 and the secondpolymer 28 for the sake of clarity of description. A third polymer, afourth polymer, fifth polymer, etc. could be used.

The natural anatomical construction of a heart valve is such that thereare anisotropic mechanical properties. The structure of the nativeleaflet is a trilayer construct. On the side facing the ventricle, thereis a layer of collagen and elastin fibers with a radial orientation(aligned from the wall of the supporting structure to the tip of thevalve leaflet). In the fibrosa layer (the side facing the aorta) thereis collagen but the fibers are oriented more circumferentially, whichimparts characteristic flexibility and enables valve sealing. It shouldbe appreciated that the composition gradient of the first and secondpolymers 26, 28 can be varied along the leaflets 14 a,b,c tosubstantially match the anisotropic mechanical properties of healthy,native leaflets.

Compared to leaflets formed of a single polymer, the compositiongradient of the first and second polymers 26, 28 can facilitateformation of thin polymeric leaflets 14 a,b,c that also exhibitstiffness characteristics similar to stiffness characteristics ofhealthy, natural leaflets. For example, the polymeric leaflets 14 a,b,ccan have a substantially uniform thickness of less than about 100 μm andexhibit anisotropic mechanical properties similar to those of healthy,natural leaflets.

Additionally or alternatively, polymeric leaflets 14 a,b,c can haveimproved durability as compared to polymer leaflets formed of a singlepolymer. For example, the flexibility of the edge portion 18 a,b,c ofeach leaflet 14 a,b,c can facilitate valve sealing (e.g., atimplantation sites having an irregular cross-sectional area as a resultof calcium deposits). As another example, the stiffness of the rootportion 16 a,b,c of each leaflet 14 a,b,c can reduce stress associatedwith movement of the leaflets 14 a,b,c into and out of coaptation withone another.

In some implementations, the composition gradient of the first andsecond polymers 26, 28 can be an increase in the ratio of the secondpolymer 28 to the first polymer 26 in a direction extending along athickness of each leaflet 14 a,b,c. In certain implementations, thecomposition gradient of the first and second polymers 26, 28 can be apattern (e.g., a sinusoidal pattern) in a direction extending generallyfrom the root portion 16 a,b,c to the edge portion 18 a,b,c.

In some implementations, the side facing the ventricle, in the implantedposition, can include only one of first and second polymers 26, 28 andthe side facing the aorta, in the implanted position, can include theother of the first and second polymers 26, 28.

The first polymer 26 is a first block polymer and the second polymer 28is a second block polymer. Each of the first and second polymers 26, 28can be a segmented block copolymer, a linear alternating multiblockcopolymer, a triblock terpolymer, or an asymetric tetrablock terpolymer.Examples of block polymers are described in Frank S. Bates et al.,Multiblock Polymers: Panacea or Pandora's Box?, SCIENCE, 336, 434(2012), the entire contents of which are incorporated herein byreference. Additionally, or alternatively, each of the block polymers isa thermoplastic elastomer. In general, the first polymer 26 and thesecond polymer 28 each have the same molecular structure and each havehard segments and soft segments. The second polymer 28 has a lower ratioof hard segments to soft segments compared to the first polymer 26.Accordingly, the first polymer 26 is stiffer than the second polymer 28.See B. Zhang et al., EUR. POLYM. J. Vol. 34, No. 3-4, pp. 571-575(1998), the entire contents of which are incorporated herein byreference.

In some implementations, at least one of the first and second polymers26, 28 is a polyurethane block polymer (e.g., copolymer) and/or apolyurethane urea block polymer, each of which can be tailored to havedesired stiffness and mechanical properties and have good bloodcompatibility. Examples of suitable polyurethane block polymers includebiostable polyurethanes such as polycarbonate urethanes (e.g.,Carbothane® available from The Lubrizol Corporation of Wickliffe, Ohio),poly(dimethysiloxane urethanes) (e.g., Elast-Eon polymers from AorTechInternational plc of Weybridge, Surrey, England), and/orpoly(isobutylene urethane). Examples of suitable poly(isobutyleneurethane) are described in U.S. patent application Ser. No. 12/492,483,filed Jun. 26, 2009, and U.S. patent application Ser. No. 12/685,858,filed Jan. 12, 2010. The entire contents of each of these applicationsare incorporated herein by reference. In certain implementations, thefirst and second polymers 26, 28 each include a soft segment that is acopolymer of a first monomer (e.g., dimethyl siloxane) and a secondmonomer (e.g., hexamethylene carbonate) and the comonomer ratio of thefirst monomer to the second monomer is varied in combination with thehard segment to soft segment ratio. In some implementations, the softsegment of each of the first and second polymers 26, 28 is hydrophilic.In certain implementations, there is an outer polymer including the samemolecular structures for hard segments or soft segments and alsoincluding an additional surface active component which can improveendothelialization or reduce calcification or both.

Referring to FIGS. 4A-C, in some implementations, the first polymer 26and the second polymer 28 each have hard segments 30 that are repeatedunits of methylene diisocyantate (MDI) and butane diol (BD) and softsegments 32 that are polytetramethylene oxide (PTMO). Comparing thestructures in FIGS. 4B and 4C, it can be appreciated that the secondpolymer 28 has a lower ratio of hard segments to soft segments comparedto the first polymer 26 and, thus, the first polymer 26 is stiffer thanthe second polymer 28.

Referring to FIGS. 5A-D, prosthetic heart valves (e.g., prosthetic heartvalve 10) are formed through one or more processes generally includingforming a base (e.g., the base 12), forming a plurality of polymericleaflets (e.g., the polymeric leaflets 14 a,b,c shown in FIGS. 1-3), andcoupling the plurality of polymeric leaflets to the base such that eachleaflet is movable to coapt with a portion of at least one of the otherleaflets. For example, a spray-coating process as shown in FIGS. 5A-Dcan be used to form prosthetic heart valves including a plurality ofpolymeric leaflets, each having a composition gradient of a first and asecond polymer along at least one portion of the leaflet.

Referring to FIG. 5A, a mold 34 (e.g., a mandrel) is positioned in avolume defined by the frame 22 (e.g., a radially expandable stent in anexpanded position) such that a leaflet form 36 of the mold 34 is at theposition at which the polymeric leaflets 14 a,b,c (shown in FIGS. 1-3)are to be formed. In some implementations, the mold 34 is moved into theframe 22. Additionally or alternatively, at least a portion of the frame22 is formed about the mold 34. The leaflet form 36 includes one or morecurved surfaces (e.g., concave surfaces) having the desired shape ofeach respective leaflet. As described in further detail below, the firstpolymer 26 and the second polymer 28 (shown in FIGS. 1-3) are sprayedonto the one or more curved surfaces of the leaflet form 36 to form theleaflets 14 a,b,c (shown in FIGS. 1-3).

Referring to FIG. 5B, a spray system 38 includes a first spray head 40,a first reservoir 42, a second spray head 44, a second reservoir 46, anda controller 48. The first spray head 40 is in fluid communication withthe first reservoir 42 to draw a first solution 26′ including the firstpolymer 26 (FIGS. 1-3) and a solvent from the first reservoir 42 to thefirst spray head 40 for application to the frame 22 and/or the mold 34.Similarly, the second spray head 44 is in fluid communication with thesecond reservoir 46 to draw a second solution 28′ including the secondpolymer 28 (FIGS. 1-3) and a solvent from the second reservoir 46 to thesecond spray head 44 for application to the base and/or the mold 34. Thecontroller 48 is in electrical communication with the first and secondspray heads 40, 44 to control, as described in further detail below, theposition of the first spray head 40 and the second spray head 44relative to the frame 22 and/or to control the volume and spray patternof the respective fluid delivered from the first and second spray heads40, 44.

The first reservoir 42 and the second reservoir 46 can each bepressurized such that the respective contents of the first and secondreservoir 42, 46 can be delivered by controlling a respective nozzleposition (e.g., open/closed) of the first and second spray heads 40, 44.The respective solvents (e.g., organic solvents) of the first and secondsolutions 26′, 28′ can facilitate achievement of a desired spray patternof the respective first and second polymers 26, 28 (FIGS. 1-3). Forexample, a lower concentration of solvent can be used in areas where itis desirable to have less flow, and a higher concentration of solventcan be used in areas where it is desirable to have flow. Additionallyalternatively, the respective solvents can have a desired viscosityand/or evaporation rate to achieve desired spreading of the respectivepolymer on the frame 22 and/or mold 34.

In some implementations, the first spray head 40 and/or the second sprayhead 44 includes one or more air spray nozzles such that the firstsolution 26′ and/or the second solution 28′ are air sprayed on the frame22 and/or the mold 34. In certain implementations, the first spray head40 and/or the second spray head 44 includes one or more electrostaticspray nozzles such that the first polymer 26 and/or the second polymer28 are electrostatically sprayed on the frame 22 and/or the mold 34. Insome implementations, such electrostatic spraying can result in theefficient transfer of the first and second polymers 26, 28 (FIGS. 1-3)on the frame 22 and/or mold 34.

The controller 48 includes a central processing unit and a memory and isin electrical communication with the first spray head 40 and the secondspray head 44 to control the volumetric emission and spatialdistribution of the first polymer 26 and the second polymer 28. Thecontroller 48 can be in electrical communication with the first andsecond spray heads 40, 44 to control movement of the first and secondspray heads 40, 44 relative to the frame 22 and mold 34. Additionally oralternatively, the controller 48 can be in electrical communication withone or more actuators to control movement of the frame 22 and mold 34relative to the first and second spray heads 40, 44.

Examples of the spray system 38 are described in U.S. Pat. No.7,335,264, entitled “Differentially Coated Medical Devices, System forDifferentially Coating Medical Devices, and Coating Method,” issued onFeb. 26, 2008, the entire contents of which are incorporated herein byreference. In some implementations, the spray system 38 is athree-dimensional printing system. For example, the three-dimensionalprinting system can produce bead-producing drops of the first and/orsecond polymer 26, 28 at controlled locations (e.g., as determined byone or more position sensors) to build up one or more surfaces (e.g.,leaflets 14 a,b,c).

An inner diameter of the frame 22 is greater than an outer diameter ofthe mold 34, resulting in a clearance 50 between the frame 22 and themold 34. The base 12 (FIGS. 1-3) is formed by spraying first and secondsolutions 26′, 28′ solutions from the respective first and second sprayheads 40, 44 such that the first and the second polymers 26, 28 (FIGS.1-3) coat the frame 22 and/or the leaflet form 36 of the mold 34. Thecoating of the first and/or second solutions 26′, 28′ on the frame 22forms the polymer layer 24 (FIGS. 1-3). Similarly, the coating of thefirst and second polymers 26, 28 on the leaflet form 36 forms the shapeof the leaflets 14 a,b,c (FIGS. 1-3).

The composition gradient of the first and second polymers 26, 28 alongthe leaflets 14 a,b,c can (FIGS. 1-3) be achieved by controlling theratio of the volume of the first solution 26′ sprayed from the firstspray head 40 to the volume of the second solution 28′ sprayed from thesecond spray head 44 along various locations along the leaflet form 36of the mold 34. Additionally or alternatively, the composition gradientof the first and second polymers 26, 28 (FIGS. 1-3) along the leaflets14 a,b,c can be achieved by controlling the thickness of the firstand/or the second solutions 26′, 28′ at various locations along theleaflet form 36 of the mold 34.

Referring to FIG. 5C, the first and/or second solutions 26′, 28′disposed over the frame 22 (FIGS. 1-3) and/or the leaflet form 36 aredried in the presence of a heat source 52. The heat source 52 can be,for example, a convective heat source such as a lamp and/or an oven. Thefirst and second solutions 26′, 28′ can be exposed to the heat source 52until evaporation of the solvents used for delivery of the first andsecond polymers 26, 28 (FIGS. 1-3) is substantially complete.

In some implementations, the first and second polymers 26, 28 areapplied to the frame 22 and/or the leaflet form 36 of the mold 34 inmultiple layers. For example, the first and second polymers 26, 28 canbe applied to the frame and/or the leaflet form 36 in a first layer, thefirst and second polymers 26, 28 can be dried, and then the first and/orsecond polymers 26, 28 can be applied in a second layer. The process ofapplying the first and second polymers 26, 28 to the frame and/or theleaflet form 36 can be repeated to achieve, for example, a desiredthickness of the leaflets 14 a,b,c (FIGS. 1-3).

Referring to FIG. 5D, a cutting element 54 is applied to the first andsecond polymers 26, 28 to form the leaflets 14 a,b,c from the first andsecond polymers 26, 28 disposed along the leaflet form 36 of the mold34. In particular, the cutting element 54 is applied to the first andsecond polymers 26, 28 to define the edge portions 18 a,b,c of therespective leaflets 14 a,b,c. The cutting element 54 can be inelectrical communication with the controller 48, with the controller 48controlling the position of the cutting element 54 relative to the firstand second polymers 26, 28.

The cutting element 54 can be a blade movable into contact with thefirst and second polymers 26, 28 disposed along the leaflet form 36 ofthe mold 34. For example, the cutting element 54 can be a single bladecontrolled by the controller 48 to cut the leaflets 14 a,b,c from thefirst and second polymers 26, 28 through a sequence of movements. Asanother example, the cutting element 54 can be three blades controlledby the controller 48 to cut the polymeric leaflets 14 a,b,c from thefirst and second polymers 26, 28 with a single motion of the cuttingelement 54.

Additionally or alternatively, the cutting element 54 can be a laser(e.g., a CO₂ laser, a femtosecond laser, or an excimer laser) directedat the first and second polymers 26, 28 disposed along the leaflet form36 of the mold. As compared to cutting with a blade, cutting the firstand second polymers 26, 28 with a laser can reduce the likelihood offraying, delamination, or other physical changes that may interfere withcoaptation of the polymeric leaflets 14 a,b,c along the edge portions 18a,b,c.

In some implementations, the mold 34 is be removed from the base 12following the drying process (FIG. 5C) and prior to cutting the leaflets14 a,b,c. In other implementations, the mold 34 remains adjacent to thebase 12 to provide support to the first and second polymers 26,28 as thecutting element 54 is applied to the first and second polymers 26,28 toform the edge portion 18 a,b,c of each leaflet 14 a,b,c.

While certain implementations have been described, other implementationsare possible.

For example, while the polymeric leaflets have been described as beinguncoated, other implementations are additionally or alternativelypossible. For example, referring to FIG. 6, for example, a surfacecoating 56 can be disposed along at least one side of each leaflet 14a,b,c extending from each respective root portion 16 a,b,c to eachrespective edge portion 18 a,b,c. It should be appreciated that, for thesake of clarity of illustration, leaflet 14 a is shown in FIG. 6 andleaflets 14 b,c (FIGS. 1-3) can be substantially identical to leaflet 14a.

The surface coating 56 can be disposed over the first polymer 26 and/orthe second polymer 28. The surface coating 56 can improve thecalcification resistance of the leaflets 14 a,b,c. In someimplementations, the surface coating 56 can facilitate maintenance ofdesirable mechanical properties and stability of the first and secondpolymers 26, 28 forming the leaflets 14 a,b,c. In certainimplementations, the surface coating can provide enhancedbiocompatibility.

In some implementations, the surface coating 56 includes hard and softsegments having the same molecular structure as the respective hard andsoft segments of the first polymer 26 and/or the second polymer 28, withthe surface coating 56 further including a small percentage of surfaceactive end groups. Having the same hard and soft segments can ensureintimate bonding with the first and/or second polymers 26, 28 of theleaflets 14 a,b,c. Examples of polymers that can be used in the surfacecoating 56 include polyurethane with surface active end groups and/orpolyurethane urea with surface active end groups. Examples include SelfAssembling Monolayer Endgroups (SAME®) available from DSM Biomedical,Berkeley, Calif., Surface Modifying Endgroups (SME®) available from DSMBiomedical, Berkeley, Calif., and Tecophilic® polyurethane availablefrom The Lubrizol Corporation of Wickliffe, Ohio. The surface active endgroups of the surface coating 56 can include non-polar surface activeend groups—e.g., one or more of fluorocarbon, dimethylsiloxane, andhydrocarbon. Additionally or alternatively, these surface active endgroups can include glycosaminoglycan and/or polysaccharide. In certainimplementations, these surface active end groups include polar surfaceactive end groups—e.g., one or more of polyethylene oxide, hyaluronicacid, and heparin. Additional or alternative examples of polymers thatcan be used in the surface coating 56 include polyurethane and/orpolyurethane urea with polyethylene oxide soft segments.

In certain implementations, the surface coating 56 is a drug-releasinglayer.

As another example, while the polymeric leaflets have been described ashaving a substantially uniform thickness, other implementations areadditionally or alternatively possible. For example, with reference toFIG. 7, leaflet 14 a′ has a decreasing thickness in a directionextending generally from a root portion 16 a′ to an edge portion 18 a′.For the sake of clarity of illustration, a single leaflet is shown inFIG. 7. However, it should be appreciated that the other leaflets mayhave the same geometry. It should further be appreciated that, unlessotherwise specified, components identified by prime reference numbers(e.g., 14 a′) are similar to the corresponding component identified byan unprimed reference number (e.g., 14 a) in FIGS. 1-3.

The thicker root portion 16 a′ can impart stiffness to the leaflet 14 a′at the point of attachment to the base 12′, and the thinner edge portion18 a′ can have increased flexibility relative to the root portion 16 a′.Such a thickness gradient, alone or in combination with a compositiongradient of the first polymer 26 and the second polymer 28, can improvedurability and/or hemodynamic performance of the leaflet 14 a′ relativeto a leaflet formed of a single polymer of uniform thickness. In someimplementations, the root portion 16 a′ is about 1000 percent thickerthan the edge portion 18 a′.

As another example, while the composition gradient of the polymericleaflets have been described as being a mixture of a first polymer and asecond polymer, other implementations are additionally or alternativelypossible. For example, referring to FIG. 8, a polymeric leaflet 14 a″includes a first layer 58 of a first polymer 26″ and one or more secondlayers 60 of a second polymer 28″. In some implementations, the firstlayer 58 is disposed between the one or more second layers 60. For thesake of clarity of illustration, a single leaflet is shown in FIG. 8.However, it should be appreciated that the other leaflets may have thesame geometry. It should further be appreciated that, unless otherwisespecified, components identified by a double prime reference number(e.g., 14 a″) are similar to the corresponding component identified byan unprimed reference number (e.g., 14 a) in FIGS. 1-3.

In some implementations, each of the first and second layers 58, 60extends in a direction generally from a root portion 16 a″ to an edgeportion 18 a″ of the leaflet 14 a″. For example, each layer 58, 60 canextend along an entire length of the leaflet 14 a″ from the root portion16 a″ to the edge portion 18 a″. The stiffness of the leaflet 14 a″ canbe varied by varying the ratio of the thickness of the first layer 58 tothe thickness of the second layer 60. For example, the thickness of thefirst layer 58 can taper downward from the root portion 16 a″ to theedge portion 18 a″, and the thickness of the second layer 60 can taperupward from the root portion 16 a″ to the edge portion 18 a″. In suchexamples, given that the first polymer 26″ is stiffer than the secondpolymer 28″, the polymeric leaflet 14 a″ can be stiffer toward the rootportion 16 a″ and more flexible toward the edge portion 18 a″.

As another example, while the prosthetic heart valves have beendescribed as being concentric (e.g., substantially cylindrical), otherimplementations are additionally or alternatively possible. For example,referring to FIGS. 9-11, a prosthetic heart valve 60 includes a base 62defining a substantially cylindrical passage 64, plurality of polymericleaflets 66 a,b,c (e.g., similar to polymeric leaflets 14 a,b,c in FIGS.1-3) disposed along the substantially cylindrical passage 64, and askirt 68 disposed about the base 62. The skirt 68 is eccentricallyarranged relative to the substantially cylindrical passage 64. Such aneccentric skirt 68 can fill the void space between the polymeric heartvalve 60 and the native valve wall and, for example, reduce thelikelihood of paravalvular leakage when the prosthetic heart valve 60 isimplanted.

The skirt 68 can include one or more polymers (e.g., the first polymer26 and/or the second polymer 28 in FIGS. 1-3). In some implementations,the skirt 68 is integral with the base 62. In certain implementations,the skirt 68 is a flap coupled to the base 62 for a lower profile (e.g.,during transcatheter delivery) and is movable into position about thebase 62 during implantation.

As yet another example, while coating processes have been described asincluding a cutting step to form edge portions of polymeric leaflets ofa prosthetic heart valve, other implementations are additionally oralternatively possible. For example, referring to FIGS. 12A-D,prosthetic heart valves (e.g., prosthetic heart valve 10) can be formedthrough one or more processes generally including dispending the firstsolution 26′ and the second solution 28′ on either side of a wall (e.g.,a shim) disposed in a volume defined by the frame 22, reducing oreliminating the need to cut the first and second polymers 26, 28 to formthe leaflets 14 a,b,c.

Referring to FIG. 12A, a mold 70 (e.g., a mandrel) includes a leafletform 72 and a divider 74 having substantially planar surfaces extendingabove the leaflet form 72. The divider 74 can be, for example, a shim.As another example, the divider 74 can have variable thickness such thatthe spacing between the leaflets 14 a,b,c (FIGS. 1-3) formed is variablein a radial direction of the with respect to the frame 22.

Referring to FIG. 12B, the mold 70 can be positioned in a volume definedby the frame 22 (e.g., a radially expandable stent in an expandedposition) such that the leaflet form 72 is at the position at which thepolymeric leaflets 14 a,b,c (FIGS. 1-3) are to be formed and the divider74 extends above the leaflet form 72. The first and second solutions26′, 28′ are applied by spray system 38 to the leaflet form 72 on eitherside of the substantially planar surfaces of the divider 74 such thatthe divider 74 separates the leaflets 14 a,b,c (FIGS. 1-3) after thefirst and second solutions 26′, 28′ have been applied.

Referring to FIG. 12C, the first and second solutions 26′, 28′ can bedried in the presence of a heat source 52 in a manner substantiallyanalogous to the drying described above with respect to FIG. 5C.However, it should be appreciated that the divider 74 is disposedbetween the leaflets 14 a,b,c (FIGS. 1-3) while the mold 70 is disposedin a volume defined by the frame 22 (FIG. 12B). Once the first andsecond solutions 26′, 28′ are substantially dry, the mold 70, includingthe divider 74, can be removed from the frame 22.

Referring to FIG. 12D, a trimming element 76 can be directed toward theleaflets 14 a,b,c to remove excess amounts (e.g., flash) of the firstand/or second polymer 26,28 left on either side of the divider 74. Thetrimming element 76 can include, for example, a blade or a laser.

As still another example, while spray coating processes for forming theprosthetic heart valves have been described as coating the frame and theleaflet form together, other embodiments are additionally oralternatively possible. For example, referring to FIGS. 13A-E, a spraycoating can be applied to the frame 22 and the leaflets 14 a,b,c can beformed separately.

Referring to FIG. 13A, a base mold 78 can be positioned within a volumedefined by the frame 22. An outer diameter of the base mold 78 is lessthan an inner diameter of the frame 22 such that a clearance 80 isdefined therebetween. The spray system 38 applies the first solution 26′and/or the second solution 28′ to the frame 22 such that the firstand/or the second solutions 26′, 28′ coats one or more surfaces of theframe 22, including filling in the clearance 80, to form the base 12. Insome implementations, one or more portions of the frame 22 are maskedwhile the first and/or the second solutions 26′, 28′ are applied to theframe 22, and the mask is later removed such that the first and/or thesecond polymer are not deposited on the previously-masked portions ofthe frame 22. The first and/or second solutions 26′, 28′ on the frame 22can be dried (e.g., by exposure to a heat source 52 as described abovewith respect to FIG. 5C) and the base mold 78 can be removed from thebase 12.

Referring to FIG. 13B, the mold 34 can be positioned along thesubstantially cylindrical passage 13 defined by the base 12. The firstsolution 26′ and the second solution 28′ can be applied (e.g., spraycoated) to the leaflet form 36 to form the shape of the leaflets 14a,b,c and couple each root portions 16 a,b,c to the base 12 (FIGS. 1-3).The first solution 26′ and the second solution 28′ can be dried (e.g.,by exposure to a heat source 52 as described above with respect to FIG.5C) and the respective edge portions 18 a,b,c of each leaflet 14 a,b,c(FIGS. 1-3) can be formed (e.g., through cutting as described above withrespect to FIG. 5D).

As yet another example, while the method of forming prosthetic heartvalves has been described as including a spray coating process, otherprocesses are additionally or alternatively possible. For example,referring to FIGS. 14A-C, forming prosthetic heart valves can includedip coating at least a portion of a mold into one or more polymersolutions.

Referring to FIG. 14A, a form 82 can be dipped into a reservoir 84containing a polymer solution 86. The form 82 can include a frame (e.g.,frame 22) and/or a mold (e.g., mold 34), and the polymer solution 86 caninclude the first and/or second polymer solutions (26′, 28′ in FIGS.5A-5C). The depth and dip rate of movement of the form 82 into thereservoir 84 can be controlled to control the distribution and thicknessof the polymer solution 86 on the form 82. Additionally oralternatively, one or more portions of the form 82 can be masked priorto dipping the form 82 into the polymer solution 86 to control thedistribution of the polymer solution 86 on the form 82.

Referring to FIG. 14B, the polymer solution 86 can be dried on the form82 by exposure to a heat source 52. Once the polymer solution 86 issubstantially dried, the form 82 can be dipped in the polymer solution86 or in another polymer solution having a different polymer and/or adifferent solvent. The process of drying polymer solutions on the form82 and dipping the form 82 in a polymer solution can be repeated toachieve a desired distribution and thickness of the first and secondpolymers 26, 28 along the base 12 and the leaflets 14 a,b,c. After afinal drying step, the base 12 can be removed from the form 82.

Referring to FIG. 14C, edge portions 18 a,b,c of each leaflet 14 a,b,care formed by directing the cutting element 54 toward the leaflets 14a,b,c.

Referring to FIGS. 15A-C, forming prosthetic heart valves can includevacuum forming the first and/or second polymer 26, 28 on the form 82. Ascompared to spray coating and dip coating, vacuum forming does notrequire drying the polymers and, thus, can reduce processing time and/orfacilitate accurate positioning of the first and/or second polymers26,28 on the prosthetic heart valve 10.

Referring to FIGS. 15A-B, a film 88 includes the first and/or secondpolymer 26,28 (FIGS. 1-3). The film 88 is vacuum formed (e.g. throughthe application of a vacuum pressure) onto the form 82 such that, asshown in FIGS. 1-3 for example, the first and/or second polymer 26, 28have the desired distribution, thickness, and/or composition gradientalong the base 12 and/or the leaflets 14 a,b,c. In some implementations,the film 88 is vacuum formed onto a portion of the form 82 to form thebase 12. In certain implementations, the film 88 is vacuum formed onto aportion of the form 82 to form the leaflets 14 a,b,c.

Referring to FIG. 15C, the cutting element 54 can be directed toward theleaflets 14 a,b,c to form the edge portions 18 a,b,c, and the form 82can be removed from the prosthetic heart valve 10.

As another example, leaflets have been described as including a firstand a second polymer having a composition gradient along at least aportion of each leaflet. However, other implementations are additionallyor alternatively possible. For example, referring to FIG. 16, a valve 90includes a base 92 and a plurality of leaflets 94 a,b,c disposed in avolume 95 defined by the base 92. Each leaflet 94 a,b,c has a respectiveroot portion 96 a,b,c coupled to the base 92 and a respective edgeportion 98 a,b,c substantially opposite the root portion 96 a,b,c andmoveable relative to the root portion 96 a,b,c to coapt with arespective edge portion 96 a,b,c of at least one of the other leaflets94 a,b,c. Each leaflet 94 a,b,c includes a plurality of fibers 100 atleast partially embedded in a polymer 102. For the sake of clarity ofillustration, the fibers 100 are shown only in leaflet 94 a. However, itshould be appreciated that the fibers 100 are also at least partiallyembedded in leaflets 94 b,c.

As described in further detail below, the fibers 100 can be orientedalong the leaflets 94 a,b,c to impart desired mechanical properties(e.g., stiffness) to the leaflets 94 a,b,c. Additionally, the polymer102 can be a combination of one or more polymers (e.g., the first andsecond polymers 26 and 28 of FIGS. 1-3) with a composition gradient ofone or more polymers along at least a portion of each leaflet 94 a,b,c,for example, to impart further desired mechanical properties to theleaflets 94 a,b,c. Fibers 100 and the composition of one or morepolymers can be arranged to impart anisotropic mechanical properties ineach leaflet 94 a,b,c.

The fibers 100 can include one or more of the following: polyester,ultra-high-molecular weight polyethylene, liquid crystalline polymer(LCP) fibers (e.g., Kevlar® available from DuPont ProtectionTechnologies, Richmond, Va., Nomex® available from Dupon ProtectionTechnologies, Richmond, Va., and Vectran® available from the KurarayAmerica, Inc., Houston, Tex.), NiTi wire mesh, graphene, carbon fibernanotubes, etc.

The fibers 100 can be at least partially embedded into the polymer 102with a controlled count and directionality to achieve desired mechanicalproperties of the leaflets 94 a,b,c. For example, each of the fibers 100can extend in circumferential direction along each respective leaflet 94a,b,c—e.g., a direction substantially perpendicular to a directionextending from the root portion 96 a,b,c to the edge portion 98 a,b,c ofeach respective leaflet 94 a,b,c. Additionally or alternatively, thefibers 100 can be embedded in each respective leaflet 94 a,b,c such thatthe concentration of fibers 100 decreases in a direction along eachleaflet 94 a,b,c (e.g., in a direction from the respective root portion96 a,b,c to the respective edge portion 98 a,b,c). This can result ineach respective leaflet 94 a,b,c having one or more anisotropicmechanical properties (e.g., stiffness). In some implementations, ahigher concentration of fibers 100 toward the root portion 96 a,b,cresults in increased stiffness of the respective leaflet 94 a,b,c towardthe root portion 96 a,b,c. In certain implementations, the fibers 100can be arranged in a cross-hatch pattern. For example, the fibers 100 ina cross-hatch pattern can be more circumferential toward the rootportion 96 a,b,c of each respective leaflet 94 a,b,c.

As another example, referring to FIG. 17, a valve 104 includes aplurality of leaflets 106 a,b,c, each having a root portion 108 a,b,cand an edge portion 110 a,b,c. Each leaflet 106 a,b,c includes aplurality of radial fibers 112 at least partially embedded in a polymer114 and a plurality of circumferential fibers 116 at least partiallyembedded in the polymer 114. The polymer 114 can include one or morepolymers (e.g., the first polymer 26 and the second polymer 28) having acomposition gradient along at least a portion of the leaflets 106 a,b,c.

Each of the radial fibers 112 extends in a direction substantiallyparallel to a direction extending generally from the root portion 108a,b,c to the edge portion 110 a,b,c of the respective leaflet 106 a,b,c.Each of the circumferential fibers 116 extends in a directionsubstantially perpendicular to a direction extending generally from theroot portion 108 a,b,c to the edge portion 110 a,b,c of the respectiveleaflet 106 a,b,c. For the sake of clarity of illustration, the radialfibers 112 and the circumferential fibers 116 are shown only in leaflet106 a. However, it should be appreciated that the fibers 112, 116 arealso at least partially embedded in leaflets 106 b,c.

While the fibers 112,116 are described as having a particularorientation, the fibers 112, 116 can be substantially randomly orientedrelative to one another. This can be useful for example, for impartingsubstantially isotropic mechanical properties to the leaflets 106 a,b,c.

Referring to FIG. 18, the fibers 112,116 (can be at least partiallyembedded in the polymer 114 by positioning the fibers 112,116 in grooves118 defined by a mold 120. The polymer 114 can be formed into theleaflets 106 a,b,c (FIG. 17) through one or more of the spray coatingand dip coating processes described above.

In some implementations, the fibers 112, 116 are preformed in a film ofpolymer 114. The polymer 114 can be formed into the leaflets 106 a,b,c(FIG. 17) through one or more of the vacuum forming processes describedabove. [0001] A number of implementations have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the spirit and scope of this disclosure. Forexample, while implementations have been described as being directed toprosthetic heart valves including a frame, other implementations can beframeless. As another example, while implementations have been describedas being directed to prosthetic heart valves including three leaflets,other implementations can include fewer leaflets (e.g., two leaflets) ormore leaflets (e.g., four leaflets). As yet another example, whileimplementations have been described as being directed to prostheticheart valves, other implementations. Accordingly, other implementationsare within the scope of the following claims.

What is claimed is:
 1. A prosthetic heart valve comprising: a base; aplurality of polymeric leaflets, each leaflet having a root portioncoupled to the base, each leaflet having an edge portion substantiallyopposite the root portion and movable relative to the root portion tocoapt with a respective edge portion of at least one of the otherleaflets of the plurality of leaflets, each leaflet comprising) at leasttwo polymers, and each leaflet having a composition gradient of each ofthe at least two polymers along at least one portion of the leaflet. 2.The prosthetic heart valve of claim 1, wherein each leaflet has asubstantially uniform thickness.
 3. The prosthetic heart valve of claim1, wherein each leaflet has a decreasing thickness in a directionextending generally from the root portion to the edge portion.
 4. Theprosthetic heart valve of claim 1, wherein one of the at least twopolymers is a first layer, another one of the at least two polymers is asecond layer, and each of the layers extends in a direction generallyfrom the root portion to the edge portion.
 5. The prosthetic heart valveof claim 4, wherein the thickness of one or more of the first and secondlayers decreases in the direction generally from the root portion to theedge portion.
 6. The prosthetic heart valve of claim 1, wherein thecomposition gradient is a substantially continuous increase in the ratioof the second polymer to the first polymer along the at least oneportion of the leaflet.
 7. The prosthetic heart valve of claim 1,wherein the composition gradient is a pattern of each of the at leasttwo polymers along the at least one portion of the leaflet.
 8. Theprosthetic heart valve of claim 1, wherein each leaflet has a stiffnessgradient along the at least one portion of the leaflet corresponding tothe composition gradient.
 9. The prosthetic heart valve of claim 8,wherein each leaflet has a composition gradient and a stiffness gradientin a direction extending from the root portion to the edge portion. 10.The prosthetic heart valve of claim 8, wherein each leaflet has acomposition gradient and a stiffness gradient in a direction extendingalong a thickness of the leaflet.
 11. The prosthetic heart valve ofclaim 8, wherein each leaflet has a maximum thickness of 100 μm or less.12. The prosthetic heart valve of claim 1, wherein each of the at leasttwo polymers has respective hard segments and soft segments and theratio of hard segments to soft segments in one of the at least twopolymers is higher than the ratio of hard segments to soft segments inanother of the at least two polymers.
 13. The prosthetic heart valve ofclaim 12, wherein each of the at least two polymers is a respectiveblock polymer, wherein the soft segments of each block polymer is acopolymer of a first monomer and a second monomer and the comonomerratio of the first monomer to the second monomer is varied incombination with the hard segment to soft segment ratio, wherein thefirst monomer is dimethyl siloxane and the second monomer ishexamethylene carbonate.
 14. The prosthetic heart valve of claim 1,wherein at least one of the at least two polymers is a polyurethaneblock polymer and/or a polyurethane urea block polymer.
 15. Theprosthetic heart valve of claim 1, wherein at least one of the at leasttwo polymers is one or more of the following: polycarbonate urethane;poly(dimethylsiloxane urethane); and poly(isobutylene urethane).
 16. Theprosthetic heart valve of claim 1, wherein one of the at least twopolymers is a surface coating disposed over at least a portion ofanother of the at least two polymers, along at least one side of theleaflet extending from the root portion to the edge portion.
 17. Theprosthetic heart valve of claim 16, wherein each of the at least twopolymers have respective hard and soft segments, the hard and softsegments of the surface coating having the same molecular structure asthe respective hard and soft segments of the other of the at least twopolymers, and the surface coating comprising surface active end groups,wherein the surface active end groups comprise non-polar surface activeend groups.
 18. The prosthetic heart valve of claim 1, furthercomprising a skirt disposed about the base, the base defining aconcentric passage therethrough, and the skirt eccentrically arrangedrelative to the concentric passage of the base.
 19. The prosthetic heartvalve of claim 1, wherein the base comprises one or more of the at leasttwo polymers.
 20. A method of forming a prosthetic heart valve, themethod comprising: forming a base defining a substantially cylindricalpassage therethrough; forming a plurality of leaflets, each leaflethaving a root portion and an edge portion substantially opposite theroot portion, each leaflet comprising at least two polymers, and eachleaflet having a composition gradient of each of the at least twopolymers along at least one portion of the leaflet; and coupling theroot portion of each of the plurality of leaflets to the base such thateach respective edge portion is substantially opposite the root portionand movable relative to the root portion to coapt with a respective edgeportion of at least one of the other leaflets of the plurality ofleaflets.